The various commercials that you watch in the beginning range from tame to disturbing. Probably the worst offender is the Bomb Shelter Buffet. It features cooks who work with animal carcasses on camera, including the chef cutting off the head of an alligator. It's Nausea Fuel all around.
Snake's opening monologue about the world driven by War Economy. Soldiers (ultimately) no longer fighting for food, money, resources, loyalty, religion, belief or ideals. They are fighting and die like flies every day simply to... keep this very cycle of killing going and nothing more. There is no one you can point to as the villain, since the person who started it is completely comatose, and you can't really blame the AIs... It went from ideology contained in a man to a concept of pure-raw evil, one that everybody accepted and lived under in daily life without realizing.
And to think this happened because of The Boss' wish to see the world in peace...
FOXDIE in Snake's body is going out of control due to worsening body condition, possibly turning Snake into walking biological weapon that kills everyone indiscriminately in the future. As if Snake has enough of himself to worry about...
Revolver Ocelot triggering mass-hysteria on SOP-equipped operators in the Middle East, resulting in massive headache followed by the PMCs uncontrollably beating each other up barehanded. Under SOP, your body is not your own.
FROGS and BB Squad are made by suppressing emotions in already mentally damaged women and make them fight. In the War Economy, even the disabled are soldiers as long as they can fire a gun.
The fight against Laughing Octopus. Octopus has a cloaking device that renders her near invisible, making night-vision pretty much your only option of seeing her. She can also go anywhere with her tentacles, meaning she could be right above you at any given moment. Also note the fact that she could disguise herself as a dead body, your pal the Mk. II, furniture, and your friend Naomi Hunter. It gets even scarier later in the fight when she does away with the tricks and starts to randomly jump out at you from the windows charging maniacally, allowing her high-damage dealing tentacles to hit you.
All of the B&B corps were freaky. Take beautiful women in what appears to be skintight latex, add horrible psychological problems and cybernetic augmentations, arm them heavily, have a scene that shows them slaughtering a dozen or so Faceless Goons and imply that they knew the Player Character was watching all along. Then in the second stage of each boss fight, you have to defeat the same women in their human form with their masks off, still in the bodysuits. If they get close enough, they can hug you to death. The repeated fetishistic shots of their feet don't help either, nor does the easter egg where you can take photos as they pose for you, in one case while one of the women is crying. Guess what the juxtapositions cause?
While most players find the Beauties' backstories full of Narm, Raging Raven and Crying Wolf have pretty realistically horrifying ones. Raven was abducted by insurgents as a child, beaten, starved, and had her flesh pecked at by hungry crows for who knows how long. Crying Wolf was escaping a war-torn African village with her infant brother, and accidentally smothered him to death while hiding from pursuers. Even worse, after that she began hallucinating and murdered every child in her refugee camp. After all of that, being put in a high-tech killing suit and forced to practically run on negative emotions sounds like the epitome of And I Must Scream.
Just a guess, going by these scenes and End of Evangelion do you think Hideo Kojima and Hideaki Anno know each other?
Never mind the constant screaming as the women stagger towards you, as the sounds of whatever trauma broke their minds play back.
Laughing Octopus is the creepiest. The others are fine. It's normal for someone in that kind of situation to scream, be angry, or even cry. Octopus just laughs the entire time. She's not even laughing at you. She's just...laughing. Even while you shoot her. And she just won't stop.
The fight against Screaming Mantis. It doesn't help that the dead are reanimated, and you're dealing with a boss that can float and teleport in a game that isn't supposed to be absurdly supernatural. The second half of the battle is, if possible, freakier; dealing with a woman slowly walking up to you while effortlessly sidestepping your attacks as the screen goes to black and white, all while hearing a chorus of screams of what must be torture victims, made it a rather distracting battle. Oh yes, and she is begging, begging, for Snake to kill her. Sweet dreams.
And then she screams after the fight... and then who should show up but Psycho Mantis?
Out of all the B&B Corps, Crying Wolf has possibly the creepiest boss theme in the game. Mournful and droning howls in the background, sounds of a harsh blizzard that sends chills down your spine, and what sounds like a distorted woman's sobs and breathing that tricks you into thinking that Crying Wolf is right besides you.
Zero's death in the ending: No matter how responsible he is for the countless atrocities and disasters caused directly or indirectly by The Patriots, watching a wheelchair-bound old man suffocate to death for several seconds as his air supply is cut off, right before he goes limp and flatlines, is not exactly pleasant.
The Gekko are extremely unsettling, on an intellectual level. Those legs aren't just nanotech synthetic muscles, they're actual cloned living ungulate tissue. They're basically two disembodied cow legs hooked up to life support, with a mini-tank on top. And after doing anything strenuous, they excrete excess lactic acid. Creepy. As. Hell.
They're very likely designed to scare and unsettle, especially considering the variety of bizarre noises they emit during combat. These range from the chirping of cicadas to the screams of cattle, the latter being particularly unsettling considering their relation to Japanese WWII air raid sirens.
There's something very human — almost feminine — about Gekko legs, but the color and size are off. The organic and inorganic nature of these things is also unsettling.
What Zero did to Big Boss: After supposedly being best friends and brothers in arms, Big Boss turned on Zero and left the Patriots. Zero's revenge? Have Snake "kill" Big Boss (in Metal Gear 2: Solid Snake), retrieve his body, and keep it barely alive on life support, using him as the only working key to his super computer network that he chose to be his successor. And if that wasn't bad enough, it turns out that Big Boss is not simply in a coma - he's actually in a permanent state of locked-in syndrome, a state maintained by the nanomachines injected into his body by the Patriots. As a result, he cannot move, speak, or do anything, but he is fully aware of his environment. Okay, he can thrash about a little bit - which only makes it worse. And of course, it turns out they did this to Solidus too.
The aforementioned "AI successors" eventually mutated their original parameters into a horrific mess of an illogical form of reproduction via... war itself. Which would gradually consume the entire world if Solid Snake and his tech buddy Otacon hadn't erased that part of the AI System.
That bit where Snake wakes up with his pixelated MGS1 head on his hi-res MGS4 body. It just drives straight into the Uncanny Valley and never leaves.
The Microwave Hallway is a combination of this and Tear Jerker.
Whenever you die in normal gameplay, not only you're treated to flashes of characters and crucial plot points of the game to signify Snake's life flashing before his eyes as he dies, but if you look closely to Snake's corpse, you can see that there are strings attached to him as if he were a puppet. Who's the puppeteer? You.
Just as well, the voice acting in this game is arguably among the best in the series. But that only makes Otacon's desperate yelling all the more harrowing upon your death. Yes, it's iconic, but here, the emotion is real. You can hear Otacon's voice cracking in despair.
. Mournful and droning howls in the background, sounds of a harsh blizzard that sends chills down your spine, and what sounds like a distorted woman's sobs and breathing that tricks you into thinking that Crying Wolf is right besides you.